A molecular and genetic study of mammalian ribosomal protein (rprotein) genes is described. The approach outlined involves well-characterized panels of mammalian rprotein cDNAs, human genomic and cDNA libraries and Chinese hamster cell ribosomal protein mutants. Four specific aims are indicated. 1. Mutant and wildtype rprotein genes will be sequenced. Differences among these structures should indicate the molecular nature of somatic mutations as well as limits of polymorphism compatible with ribosome assembly and function. 2. Fourteen ribosomal genes (for which cDNA probes are available) will be mapped on human chromosomes using appropriate human x rodent cell hybrids. Chromosomal organization of rprotein genes can provide clues to mechanisms regulating the gene family and to its evolutionary history. 3. The arrangement and nucleic acid sequences of several human and other species' rprotein genes will be determined. Structures shared by heterologous human genes can suggest mechanisms that regulate the gene family. Differences among analogous genes from phylogenetic series of animals should permit construction of a ribosomal protein gene evolutionary history. 4. rProtein cDNA probes and genomic DNA clones will be used to analyze transcription, messenger processing and mRNA turnover in cultured animal cells. In particular, effects of gene dosage and organization on ribosomal gene regulation will be investigated.